Method for treating benign and malignant tumors utilizing radio frequency, electromagnetic radiation

ABSTRACT

A method of treating tumors, both benign and malignant, such as carcinoma, sarcoma, cysts and avascular lesions, in animals, such as humans, by radio frequency heating at the location of the tumor in the host with intensity and duration sufficient to cause necrosis of the tumor tissue. Substantial damage to the surrounding normal tissue is avoided, as the surrounding normal tissue is cooled by blood flow which carries the heat away to dissipate such heat in those portions of the body not being subjected to heating.

RELATED CASES

This application is a continuation-in-part of LeVeen application Ser.No. 595,094, filed July 11, 1975 now abandoned, which is in turn acontinuation-in-part of LeVeen application Ser. No. 436,102, filed Jan.24, 1974 (now abandoned), and is related to LeVeen application Ser. No.595,095, filed July 11, 1975 (now abandoned).

This invention relates to the treatment of tumors in animal hosts, suchas human beings, and in particular provides a technique for destroyingthe tumor without injury to adjacent normal tissues. The tumors can beeither benign or malignant and include carcinomas, sarcomas, cysts andavascular lesions.

It is an important object of this invention to provide a methodapplicable to the treatment of tumors under a wide variety of conditionswhich can be utilized with a minimum, and preferably an absence, ofsurgery.

It has been noted that tumors can be affected by hyperthermia (Brit. ofCancer 25:771, 1971; Cancer Research 32:1916, 1972). This observationwas coupled with the statement that the tumors were heat sensitive.Experiments with external surface heating do not produce deep heatingand in some cases, using hyperthermia, the whole animal was heated asmuch as the tumor. Others have felt that a slight raise in temperaturesproduced by metabolic changes in the cancer interfered with cell growth(Europ. J. Cancer 9:103, 1973). Others have heated tumors for a fewdegrees by diathermy to observe the effect on the tumor which wasinhibitory but not obstructive (Zeit, fur Naturforschung 8, 26:359,1971). There is still considerable disagreement and conflicting evidenceof the role heat may play in the treatment of cancer (The Lancet, May 3,1975; 1027).

Anatomical studies suggest that the blood flow through carcinomas andother neoplasms is sluggish (Acta Pathalogica Microbiologica Scand.,22:625, 1945; Advances in Biology of the Skin, 21:123, 1961). Tumorspossess an angiogenetic factor which initiates the formation of newblood vessels. These blood vessels, however, are capillaries whichbecause of their small diameter offer great resistance to blood flow.The capillaries make connections with the normal capillaries on theperiphery of the tumor and are tortuous following haphazard pathwaysbefore emptying into some small vein at the periphery of the tumor.Frequentlyl there is marked venous obstruction within the tumor causedby compression of the peripheral veins due to enlargement of the tumorand sometimes due to ingrowth of tumor cells into the blood vesselsobstructing them.

Anatomical studies also demonstrate the presence of arterio-venousfistulae at the periphery of tumors which can cause the tumors to appearvascular and angiography because of the rapid appearance of contrastmedia, but which actually deprive the tumor of the blood supply. Thearterio-venous fistulae at the periphery of the tumor tend to create alow resistance pathway at the surface of the tumor which lowers thearterial pressure and diverts blood from entering the tumor.

Although anatomical studies suggest that the tumor blood flow isdiminished and slow, only angiographic studies have functionallyconfirmed that blood flow through tumors is actually sluggish givingrise to an appearance of non-filling on angiography. Residual contrastmedium remains in the tumor after it has been swept out of the adjacentnormal tissue by normal blood flow. This remaining residual contrastmedium has been called a "Tumor Stain." The tumors which have beenstudied radiographically have been brain tumors and kidney tumors.

This has been confirmed by the applicant by the indicator dilutiontechnique measuring the actual flow of blood through normal tissue andthrough tumors. The indicator dilution technique is more reliable thanthe visual method as seen on angiography. Such studies were done in vivousing X-ray contrast medium dilution and in vitro on excised specimens.In the excised specimens blood flow was measured by indicator dilutiontechnique using radioiodinated serum albumin. The albumin molecule wastagged with I₁₃₁ and the isotope dilution was measured in the tumor andin normal tissue by a columnated scintillation counter. These studiesindicated that the magnitude of flow through the adjacent normal tissueis such that the tumor tissue is differentially heated when the area ofthe body containing the tumor is treated by diathermy.

In accordance with this invention, tumors are destroyed in humans andother animals by heating the portion of the body containing the tumorsuch that the temperature of the tumor is raised to a point at which thetumor is necrosed, i.e., at or above about 50° C. In some instancesnecrosis of the tumor is achieved at temperatures as low as 46° C. Suchtemperatures, of course, also destroy or severely damage normal tissueand the present invention is based on the discovery that when a portionof the body is heated, for example, by applied radio frequencyelectromagnetic radiation, the tumor is heated differentially to agreter extent, such that the temperature of the normal tissue adjacentthe tumor can be kept below 40° C.

This is caused primarily by the normal blood flow in the adjacent normalnon-cancerous tissue. Thus, the temperature at which tissue is heateddepends upon the blood supply to the tissue. Although the blood itselfis heated, it serves to carry heat away from the part being heated. As aresult, tissues which are poorly perfused with blood become heated morerapidly and to a higher temperature than tissues which have a normalrate of blood flow. As pointed out above, cancerous and other malignantand benign growths develop outside a preformed blood vessel distributionnetwork and derive their blood supply from the periphery of the tumorwhere it meets the adjacent normal blood supply. As a consequence, theslow rate and volume of blood flow through the tumor provides a lessercooling rate in the tumor than the flow of blood through the normaltissues adjacent the tumor.

Thus, when, for example, diathermy is applied in vivo to tissuecontaining a tumor, the tumor is heated more than the adjacent normaltissue. If the applied radiation is of sufficient intensity and for asufficient duration of time the differential heating of the tumor cannecrose the tumor without significant thermal injury to the adjacentnormal tissue.

In accordance with this invention diathermy can be used to producedifferential heating of cancerous tissue in the body. Insulatedapplicators, which are connected to the output of an R.F. generator, areplaced on opposite sides of the portion of the body adjacent thelocation of the tumor such that the applicators produce localizedheating in the tumor differentially higher than the remaining normaltissue, adjacent to the tumor, which is in the path of the R.F.radiation, i.e., generally between the applicators. Heating the tissuebetween the applicators is continued for a duration of time and at anintensity sufficient to cause necrosis of the tumor by heating the tumorto about 50° C. or above. In some cases tumor necrosis can be caused byheating to temperatures as low as 46° C. In any event heating isinsufficient to raise the temperature of the surrounding normal tissueto cause significant damage to that tissue because such adjacent tissueis cooled by its normal blood supply.

This effect of destroying tumors by differential heating has beenconfirmed in both human cancers and cancers in animals by simultaneousmeasurement of the temperature in the tumor and in the adjacent normaltissue. Differential thermometry between the tumor and normal tissue isperformed with non-metallic thermometers having non-electrolyte fluids,such as liquid alcohol filled thermometers. Normal tissue isirreversibly damaged at temperatures above 50° C. (Chic. Med. Sch. Q17:49, 1956). Temperatures as high as 60° C. can easily be achieved inthe tumor while the adjacent normal tissue is heated only to thevicinity of 40° C. using about 100 watts of energy at 13.56 MHz.

Generally, the radio frequencies employed should be as low aspermissible in order to enhance the absorption of the energy by thetissue. Consequently, the lower frequencies permitted by the F.C.C. arepreferable. Since most tumors are located within the body, penetrationof the heating radiation through the location of the tumor is essential.It is well known that penetration of the body by electromagneticradiation and absorption of the energy of that radiation is an inversefunction of frequency. Generally, the practical frequency range for useof diathermy as described above to produce internal heating which can beutilized in the treatment of tumors in accordance with this invention isfrom about 100 kiloHertz to about 200 megaHertz. As in this range thelonger wavelengths are both more effective in terms of heating and lesslikely to cause damage by scattering and the like, as occurs in themicrowave region, the preference is distinctly for the longerwavelengths. The preferred frequency for treatment is 13.56 megaHertzbecause it is the longest wavelength presently permitted by law.

With impedance matching the results of this invention are generallyachieved with energies ranging between 50 and 250 watts and for periodsof times typically of 10 to 20 minutes, although lower and higher powerlevels and longer and shorter periods of time can be used depending onthe size and location of the tumor. The conventional diathermy machinecan not provide the necessary heat and has the disadvantage that thedistribution of heat in the tissues is apt to be non-uniform and can notalways be predicted. Also a considerable amount of energy on thestandard diathermy machine is often reflected back into the diathermymachine without entering the tissue. Thus, it is difficult to determinethe dosage. Utilizing the energies required in accordance with thisinvention, the conventional machine itself and the cables becomes veryoverheated. These problems are readily overcome utilizing higher poweroutput R.F. generators and heavier cables so that energies on the orderrequired can be applied to the portion of the body under treatment.Generally, the construction of suitable R.F. generators and transmissioncables are not unlike those utilized in industry for relatively lowpower outputs, i.e., on the order of 1 kilowatt in the frequency rangeunder consideration. While such a power level is high for diathermy use,it is not uncommon in many other applications, including radiotelephony,induction heating, and the like. The basic equipment is thusconventional.

It is preferred in present usage to employ an applicator generallyhaving the shape of a paddle, i.e., having a handle and a round platemore or less coplanar with the end of the handle. The plate itself is aconductive metal disc which is coated with an insulating film ofnon-glossy material, such as a coating of polyurethane resin, and isconnected to the power source through the handle of the applicator.Suitable applicators which have been used have copper plates 2 inches to4 inches in diameter. Also flat copper spirals have been used withsuccess. The leads to the applicators from the power amplifier, ofcourse, are necessarily insulated and preferably are shielded cables,such as coaxial cables, with the outer shield grounded, as peak voltageson the order of 300 volts are developed in the output circuit of theR.F. amplifier. The applicators and cables should be waterproof and besterilized before use.

The applicators are connected across the radio frequency output in thepresent usage of an amplifier capable of up to 2000 watt output. Theimpedance of the load, i.e., the body portion between the applicators,is of course variable, thus, the normal impedance matching proceduresutilized in coupling the output circuits of an R.F. generator through atransmission line to a load can be utilized. The transmission line,i.e., coaxial cables, are connected appropriately at the output tankcoil or otherwise in the final stage of the R.F. generator to provide aproper impedance match to the transmission line and impedance matchingof the end of the transmission line, i.e., the applicators, to the loadis important. In some circumstances, it has been found feasible to usefixed impedance matching at the applicators by building seriesinductance in the handles of the applicators, but this is not necessaryas separate adjustable provision for matching the load can be utilized.Without proper impedance matching the power requirements are muchgreater and damage to the R.F. amplifier can occur.

Although it is not essential in carrying out the process of thisinvention, desirably in a sophisticated unit, provision is thus made formeasuring both forward and reflected power. Similarly, fail-safeprecautions should be utilized to prevent a control failure resulting inapplication of full load of the R.F. generator to the applicators whenonly a partial load is desired.

Selective heating of tumors in accordance with the present inventionutilizing radio frequency electromagnetic energy can be furtheraccentuated by the use of drugs. Vasodilators increase tissue bloodflow, but reduce the blood flow to tumors and further decrease the tumoroxygen tension (Acta Radiol 58:401-434, 1962; Cancer 20:60-65, 1967).The use of vasodilators in connection with radio frequency treatment inaccordance with the present invention should be of beneficial effectboth because of the increased flow produced through contiguous normaltissue will better dissipate heat generated by the radio frequencyenergy while the slower flow through the tumor will accentuate theelevation of the tumor temperature.

It has also been noted that with hypotension, perfusion of blood througha tumor ceases and the tumor blanches (J. Natl. Canc. Instit.12:399-410, 1951). Consequently, the use of hypotensive agents canimprove the effects of radio frequency treatment in accordance with thepresent invention. Similarly, radiation, tumor embolism, alteration ofblood viscosity and compression can all be used to advantage.

When the tumor tissue has been necrosed it becomes a fluid. This fluidmay be removed naturally by the body but aspiration has also been founddesirable at times. Care should be taken to prevent sepsis and the useof antibiotics may be indicated.

Treatment in accordance with the present invention should be with careto avoid overheating normal tissues such as cartilage which have noblood supply. The presence of bile in the gall bladder may also cause aproblem when treatment requires application to a portion of the bodyincluding the gall bladder.

For a more complete understanding of the practical application of thisinvention, reference is made to the appended drawings in which:

FIG. 1 is a block diagram indicating an apparatus set-up for carryingout the process of this invention;

FIG. 2 is a plan view of an applicator suitable for carrying out theprocess of this invention;

FIG. 3 is an enlarged, fragmentary section taken at line 3--3 in FIG. 2;

FIG. 4 is an end view of a portion of another applicator suitable forcarrying out the process of this invention;

FIG. 5 is an elevational view of the applicator shown in FIG. 4indicating its use in relation to the portion of the body being treated;and

FIG. 6 is an electrical schematic diagram of the applicator shown inFIGS. 4 and 5.

Referring to FIG. 1, a simple arrangement of apparatus for carrying outthe process of this invention involves an exciter 10, a power amplifier20, and a pair of applicators 30. Both the exciter 10 and poweramplifier 20 are conventional. Exciter 10 has a crystal controlledoscillator, in the illustrated case operating on 13.56 mHz. Exciter 10has an output of between 2 watts and 110 watts dependent on the bias ofthe oscillator; the less negative the bias the higher the output ofexciter 10. An oscillator variable bias supply 40 functions to controlthe bias and the oscillator and hence the output of exciter 10.

Power amplifier 20 is designed to amplify the output of exciter 10, andto this end the output circuit of exciter 10 is connected to the inputcircuit of power amplifer 20 as denoted by the reference numeral 11.Power amplifier 20 is designed for an output of 30 watts to 1,000 wattsdependent upon the output of exciter 10, and, of course, is tuned to thesame frequency of 13.56 mHz.

The output circuit of power amplifier 20 is connected to energizeapplicators 30 by means of coaxial cables 21. Cables 21 have their innerconductors 22 connected across the tank circuit of the output of poweramplifier 20 and lead to applicators 30, as more fully described withrespect to FIGS. 2 and 3. As shown in FIG. 2, each coaxial cable 21includes a central conductor 22 which is provided with insulation 23over which there is a braided shield 24 and an outer jacket 25. The twoconductors 22 are connected across the tank coil in the output circuitof power amplifier 20, or optionally one can be grounded. In eithercase, the two shields 24 are grounded at the power amplifier, and, asshown in FIG. 1, are preferably also provided with an interconnection 26between shields 24 adjacent the handle 31 of each applicator 30.

Generally applicators 30, as can be seen best in FIG. 2, are in theshape of a paddle having a handle 31 and an applicator portion 32.

Each handle 31 is made of insulating material, such as a phenolic resin,and, as can be seen best in FIG. 3, is hollow such that coaxial cable 21is brought into the end of handle 31. The applicator portion 32 issecured to handle 31 at the end of handle 31 opposite that into whichcable 21 leads and is in the form of a flat, circular copper disc 34which is electrically connected at its periphery adjacent the end ofhandle 31 to the end of conductor 22.

As illustrated in FIG. 3, copper plate 34 is provided with an insulatingcoating 35 such that electrical contact with plate 34 can only be madethrough conductor 22. Coating 35 should be of non-lossy insulatingmaterial in order to minimize the generation of heat in the insulationitself. Suitable insulation materials are characterized by lowdissipation factors generally below about 0.01, and can be, for example,Mycalex (a proprietary glass and mica insulating material),polyethylene, polytetrafluorethylene, polystyrene, and polyurethanes.Polyurethanes are particularly desirable since they are readily appliedas liquids which set to form smooth, even and thin coatings.

Applicators 30 should have diameters such that when the portion of thebody containing the tumor is placed between them they will besufficiently large to place the entire tumor within the densest portionof the electromagnetic field set up when they are energized. It will beapparent that, as described above, applicators 30 function electricallyas a capacitor such that the portion of the body between the electrodesis effectively between the plates of a capacitor. Heating occurs eventhough the body tissue is basically an electroyte rather than adielectric material. The electric and magnetic fields which are set up,however, are those which would be set up between condenser plates.

It has also been found that heating in accordance with this inventioncan be obtained where the applicator structure is basically aninductance. Thus, referring to FIGS. 4, 5, and 6, there is shown anapparatus for developing and directing a radio frequency electromagneticfield in one direction with the energy confined to a desired region forlocalized heating of, for example, body tissue. The basic apparatusinvolves three essentially identical circuit units 50, 60, and 70.

Each unit 50, 60, and 70 includes a pancake coil 51, 61, and 71,respectively, which is in the form of a planar spiral of flatsilver-plated copper having three turns from the inner to the outer end.Variable (0-250 pf) vacuum capacitors 52, 62, and 72 are respectivelyconnected across each spiral coil 51, 61, and 71. Each spiral coil 51,61, and 71 is housed in a circular polytetrafluoroethylene (PTFE) disc53, 63, and 73, respectively, which is grooved appropriately to receiveits associated spiral coil 51, 61, and 71 with the connections of suchspiral coil extending from the PTFE disc for connection to itsassociated vacuum capacitor 52, 62, or 72. The open side of each PTFEdisc, i.e., the side in which grooves are machined to receive theassociated spiral, is covered with a thin plate of Mycalex 54, 64, and74 to retain the associated spiral coil 51, 61, and 71, respectively,within its associated PTFE housing.

Unit 50 has its spiral coil 51 and capacitor 52 connected in parallelacross the output of an R.F. power amplifier, such as amplifier 20, andis considered as the driver section which sets up an electromagneticfield when energized by power amplifier 20.

Unit 60 is mounted on a common housing of dielectric material with unit50 such that they are parallel to each other and axially aligned spacedapart 6 inches when using a frequency of 13.56 mHz to energize unit 50.As a result, the electromagnetic field developed by unit 50 whenenergized is actually directed with regard to its magnetic componentaxially toward and through unit 60 (to the right as shown in FIG. 5).For convenience sake, unit 60 may be regarded as a focus section.

Unit 70 is positioned parallel to unit 60 and axially aligned with it onthe side of unit 60 opposite unit 50 and functions as a reflectorsection confining the electromagnetic field such that an object placedbetween units 60 and 70 can be heated by the electromagnetic radiationbetween units 60 an 70. These units are then utilized in accordance withthis invention in the same manner as applicators 30. At a frequency of13.56 mHz, spiral coils 51, 61, and 71, each, can have three turns withan overall diameter on the largest turn of 5.5 inches and with the turnsspaced about 3/8 inch on center. The distance between units 60 and 70can be from 5 to 15 inches to accommodate the portion P of the doby tobe treated.

In utilizing the arrangement of FIGS. 4, 5, and 6, the driver unit isadjusted by adjusting capacitor 52 into resonance with spiral 51. Theimpedance of the unit as described above should be about 50 ohms at thispoint. Units 60 and 70 are also adjusted by means of their associatedcondensers 62 and 72 to resonance and maximum loading.

The above adjustments can all be made at a relatively low power output.The body portion P to be treated is then positioned between units 60 and70 and the desired power output of amplifer 20 is then turned on totreat body portion P. In the following discussion, where the word"applicators" is used, reference is intended to applicators, such asapplicators 30, and equally to applicators, such as units 60 and 70,unless the context clearly indicates otherwise.

Preferably, the applicators are placed firmly and in intimate contactwith the surface of the body portion under treatment in order tominimize "hot spotting" which can occur when the surface of the body isof irregular contour. Indeed, such hot spotting is further minimized byusing electrode paste on the surface of the portion of the body undertreatment, and bronze wool or woven stainless steel in the form of asleeve can be placed over the applicator further to minimize the effectsof skin resistance. Such a sleeve typically is on the order of one-halfto one inch thick, is compressible, and hence, takes up any irregularityon the surface contour of the body. Intimate contact, however, is notessential and in using fixed-tuned applicators it has been found that onoccasion more effective results have been obtained by backing one of theapplicators away from the surface of the body where the portion undertreatment was relatively narrow and not optimum for the particularapplicator.

Tissue temperatures during therapy can be determined by inserting intothe tissue being heated non-metallic thermometers having non-electrolyteindicator fluids, such as glass alcohol thermometers. It is essentialthat during therapy the adjacent normal tissue temperature be raisedonly to 40° C., as higher temperatures can cause its destruction aswell. With increased skill, a surgeon can avoid the necessity of usingthermometers, as he can sense the temperature of the normal tissue bypalpation when the diathermy is turned off. In order to destroy thetumor it is usually essential that its temperature be raised above 50°C. In some instances the tumor tissue can be necrosed at temperatures aslow as 46° C. Destruction of the tumor can be observed either bythermometric means, by X-ray techniques used to sense the presence ofthe tumor, biopsy and the like.

In some instances, for example, cancer in some human organs, such as theliver, is treated by surgically exposing the organ to place theapplicators directly in contact with the organ at the location of thecancer.

In the case of human lung carcinoma, both metastatic and primary, theapplicators can be applied to the external chest wall. Massive necrosisof the lung tumor can induce complications of pulmonary abscess orhemorrhage, but these can be dealt with surgically after all the tumorhas been destroyed.

Similarly, it may be necessary to divert the fecal stream with aproximal defunctionalizing colostomy, when rectal and colon tumors aretreated to avoid the danger of necrosis with perforation.

Other avascular lesions occurring in otherwise normal tissue willrespond equally to this therapy. Similarly, polycystic kidneys can betreated, since the cysts have no blood supply they will be heated whilethe vascular kidney substance will remain cool. Thus, the therapy willdestroy the lining of the cyst wall which secretes fluid and causescompression atrophy of the normal kidney.

EXAMPLE I

A 67 year old white male had an unresectable carcinoma of the left lungwhich proved on biopsy to be a squamous cell. He had mild dyspenea anddull pain on the left side of his chest and a brachial neuralgia.

The apparatus generally described with reference to FIG. 1 was utilized,and applicators 30 were in the form of a pair of copper plates 34 offour inch diameter and one-eighth inch thickness. The applicators werefixed-tuned by incorporating in series between the connection ofconductor 22 and plate 34 a coil located within handle 31 whichconsisted of six turns of 20 AWG copper wire with a one-half inchoutside diameter (wound about a pencil) and one-half inch in length. Thecoil and its connections to conductor 22 and plate 34 were potted usingsilicone rubber composition within handle 31. Coaxial cable 21 was ofthe type known as RG 58-U and was three feet in length in each case.Insulated coating 35 was 4 mils thick and was a clear polyurethane resincontaining no oxides.

The applicators 30 were positioned one flat against the anterior and theother flat against the posterior of his chest to position the tumorbetween them. The patient was given general anesthesia and theapplicators 30 were energized at an indicated power level of 200 wattsfor 20 minutes at 13.56 mHz. The voltage (R.M.S.) across applicators 30at this level was 100 volts. No measures were taken to insure intimatecontact with the skin and applicators 30. Consequently, a skin burnresulted.

Three days later a thoracotomy was done to biopsy the lesion. The entiretumor was incised and a large biopsy taken. This biopsy was reported asinflammatory reaction only, although the surgeon was sure he had incisedthe tumor. Subsequently, the patient's course has shown gradualimprovement. His brachial neuralgia has cleared and his chest X-rays areimproved. The treatment resulted in considerable necrosis of the chestwall. This has now healed completely.

EXAMPLE II

In this Example the patient was a 57 year old white male who hadundergone total laryngectomy for carcinoma of the vocal cordsapproximately two years before treatment. Approximately four monthsbefore treatment, the patient developed a large mass the size of anorange (3 inches in diameter) over the manubrium of the sternum(breastplate bone). Biopsy showed it to be a sqamous cell carcinoma.

The tumor was irradiated (Cobalt) but there was no substantialimprovement and no reduction in the size of the mass. He was deemedinoperable by thoracic surgery. The tumor mass was stoney hard; the skinoverlying the mass was stretched and shiny; and the tumor has pushed thetracheotomy to the right. There was also invasion of the underlyingbone. The patient was having respiratory difficulty because the tumorcompressed the trachea and his situation was desperate.

This patient was given four treatments utilizing generally the apparatusshown in FIG. 1 with the four inch applicators 30 described above inExample I. Prior to positioning the applicators, the skin of the patientwas moistened with EKG jelly to decrease skin resistance, and a bronzewool sponge was placed over the location of the tumor on each side tomaintain even electrical contact. One applicator 30 was then placed flatagainst the bronze sponge over the tumor with the second applicator 30placed flat against the midaxilla. Thus, in effect, the patient's bodywas positioned between the two applicators 30 such that the tumor waslocated between them.

Indicated power was initially raised gradually to 300 watts (about 120volts R.M.S. at 14.56 mHz) and maintained for 20 minutes between 275 and300 watts.

One week later, the hard mass has become softer and fluctuant in parts.Ten days after the treatment the mass was aspirated and semi-liquid,necrotic material was withdrawn. In order to further liquify thenecrotic material Bovine fibrinolysin and desoxyribonuclease wereinjected into the tumor. Two days later, the tumor was again aspirated.

Nineteen days after the first treatment, the patient was given a secondtreatment with the four inch applicators 30 again placed in the samemanner except that the second applicator was placed on the back of thechest to the right of the midline. Treatment was for 20 minutes. Againthe indicated power was gradually increased this time to 385 watts (135volts R.M.S. at 13.56 mHz) and then varied between 350 and 410 wattsduring the remainder of the therapy.

Two weeks later, the tumor was aspirated again. Liquid material wasobtained and the tumor was decreased considerably in size. No viabletumor cells were shown. There were some autolyzed cells. The thirdtreatment immediately followed such aspiration and was similar to thefirst treatment except that initial power was 135 watts which wasincreased to 235 watts (108 volts R.M.S. at 13.56 mHz) and continued fora total of 11 minutes.

Although further therapy was considered superfluous, since the tumor hadalready been destroyed, a fourth treatment was given ten days later. Inthis instance, applicators 30 were placed one on the midaxilla, asdescribed above, and the other first to the right and then to the leftof the tumor. In each case, the skin was moistened with EKG jelly andbronze wool sponge is placed against the skin beneath the applicator 30to maintain even electrical contact. The treatment was at 475 watts (150volts R.M.S. at 13.56 mHz) on the left side for 20 minutes and at 375 to400 watts (138 volts R.M.S. at 13.56 mHz) on the right side for 20minutes.

The final pathological diagnosis indicated no malignancy. The mass hasalmost completely disappeared although there is some inflammation and anulcer under the site of the necrotic tumor.

Before treatment in accordance with this invention the patient washaving severe respiratory difficulty because the tumor was closing offhis trachea just below the site of the tracheotomy. Since the treatment,the patient can breathe freely and has had no respiratory difficulty.Therapy in accordance with this invention resulted in minimal necrosisof the stretched skin over the lesion which will require futuregrafting.

EXAMPLE III

In this case the patient had what was considered to be a large,inoperable carcinoma of the lung which filled the entire right upperchest. The tumor mass was larger than the 4 inch applicators 30 whichare available. One applicator 30 was put on the anterior portion of thechest wall after moistening the skin with conductive paste, and theother applicator 30 was similarly positioned on the posterior of thechest wall, such that the tumor mass was largely positioned betweenthem. Fluoroscopy was utilized to define the location of the tumor mass.The patient was not anesthesized.

The apparatus was turned on to apply an indicated 50 watts and thenincreased to 256 watts (112 volts R.M.S. at 13.56 mHz) over a threeminute interval. Power was then gradually decreased to 175 watts (90volts) for the remainder of the period of 20 minutes.

Four days later the second treatment was given to the patient with thesame positioning of applicators 30 in which power was graduallyincreased over a 9 minute period to 215 watts (105 volts) and thenslowly lowered to 185 watts for 1 minute. The power level was thenincreased to 375 watts and kept for a four minute interval andthereafter between 300 and 350 watts for the rest of the 20 minutes.Because of the size of the applicators, the treatment was consideredspacially inadequate to reach the entire tumor.

Five days later a right upper lobectomy was done. The entire right upperlobe was necrotic with severe inflammatory reaction. The entire lobe wasfixed and cut on a large microtone. Ninety-nine percent of the tumor wasnecrosed but a small rim of tumor was still present where theapplicators had not completely covered the tumor. All of the treatedarea was entirely free of tumor, as the tumor in the treated area wasdead and undergoing autolysis.

In this case the inoperable carcinoma was considered to have been madeoperable since the tumor tissue adherent to the pleura and chest wallwas completely necrotic and the lesion could be removed without leavinglive tumor.

In each of the preceding Examples, the apparatus did not have provisionfor adjustable impedance matching or for measurement of forward andreflected power. The power levels indicated were based on input to thefinal stage of the amplifier and were probably two or three times thatactually applied to the body being treated.

MEASUREMENTS OF TUMOR TEMPERATURE

Temperature recordings were made in human tumor tissue before and duringR.F. therapy in six patients. Oral temperature was also recorded. Inthree patients, the temperature of the tissue adjacent to the locatedtumor tissue was also recorded. Temperature measurements were performedin those patients whose tumors were accessible to a needle typetemperature probe. The t° recorded in the tumor before and during R.F.treatment and body temperature is shown in Table I. The mean temperaturefollowing R.F. treatment was significantly higher than that beforetreatment (p<0.001) and that of body temperature (p<0.001).

                  TABLE I                                                         ______________________________________                                        Temperature Elevation With R.F. (C.°)                                        A. Max. Body                                                                              B. Tumor  C. 1° during                                                                    D. Normal                                      T° during                                                                          Prior     R.F.     Adjacent                                 Patient                                                                             R.F.        R.F.      Treatment                                                                              Tissue T°                         ______________________________________                                        1     37.5        39.1      48.0     --                                       2     38.5        37.2      48.5     40.0                                     3     38.0        38.0      49.5     --                                       4     38.2        38.0      48.5     39.7                                     5     36.0        37.2      46.0     --                                       6     37.0        37.6      49.0     --                                       7     37.1        37.2      49.5     39.0                                     Mean  37.5        37.9      48.4     39.5                                     ______________________________________                                    

Statistical analysis. Standard p test for paired data. C vs. A, t=23.58p<0.001; C vs. B, t=19.80 p<0.001.

Administration of Hypotensive Agents

As indicated above, inducing hypotension during treatment is useful inaccentuating the differential heating of tumor tissue exposed to radiofrequency electromagnetic radiation in accordance with this invention.The use of vasodilators, vasodepressors, anti-hypertensive agents andalpha blocking agents reduces the blood flow through the tumor. Typicalagents which can be used are trimethaphan camsylate, erithrityltetranitrate, amyl nitrate, and phentolamine. In inducing hypotensionduring radio frequency treatment in accordance with the presentinvention, the following procedure is suggested:

Hypotension is maintained at a level of about 60-70 mm. of mercury forthe duration of a non-half hour radio frequency treatment. The toleranceof patients varies from individual to individual and some individualscan easily tolerate hypotension of 50 mm. of mercury for thirty minutes.Care is exercised to keep the head low especially if the part to betreated is elsewhere than the head. When trimethaphan camsylate.(Arfonad) is the hypotensive agent, one ampule of 10 ml. of Arfonadcontaining 50 mg. per ml. is diluted to 500 cc. in 5% glucose indistilled water. An intravenous drip is started and the initial rate ofadministration given is 60 drops per minute. The blood pressure is takenevery five minutes during the administration of the hypotensive agent.There is a marked variation in the patient's response and the rate ofinfusion must be frequently adjusted to maintain the blood pressure atthe desired level. If there is any evidence of fainting or cerebralanoxia, the infusion is slowed and the blood pressure is allowed to comeup to a higher level. In thin patients, the rate of drug administrationcan be as slow as four drops per minute, while in other patients, 100drops per minute is sometimes required. Therefore, the blood pressure isused as an indication of proper dosage rather than the total amount ofdrug which the patient receives. The blood pressure promptly returns tonormal upon cessation of the drug although the return toward normal canbe hastened by the administration of vasopressor drugs.

I claim: .[.1. A method of treating a naturally occurring tumor in ahuman which comprises placing the portion of the body of the human inwhich the tumor is located in a radio frequency electromagnetic fieldthereby to heat the tumor tissue in said portion of said body byabsorption of energy from said radio frequency electromagnetic field fora period of time and with intensity sufficient to cause necrosis of saidtumor, but insufficient to cause significant damage to the adjacentnormal tissue in said field..].
 2. The method of claim .[.1.]. .Iadd.9.Iaddend.in which the body portion is placed in a radio frequency fieldby positioning insulated, conductive metal plates in intimate contactwith the portion of the body containing the tumor such that the tumorlies between the conductive metal plates, and applying radio frequencyelectrical power across said plates.
 3. The method according to claim 2in which the power level of radio frequency electrical power appliedacross said conductive metal plates is between 50 and 250 watts, inwhich the time of application is between 10 and 20 minutes and in whichsaid plates are from 2 to 4 inches in diameter.
 4. The method accordingto claim .[.1.]. .Iadd.9 .Iaddend.in which the temperature of said tumortissue is raised above 46° C. and in which the temperature of the.Iadd.adjacent .Iaddend.normal tissue .[.adjacent the tumor.]. is keptbelow 40° C. .Iadd.5. A method of treating a naturally occurring tumorin a human which comprises placing a portion of the body of the human inwhich the tumor is located in a radio frequency electromagnetic fieldranging from 100 kilohertz to 200 megahertz, heating the tumor tissueand adjacent normal tissue in said portion of said body by absorption ofenergy from said radio frequency electromagnetic field for a period oftime and with intensity sufficient to heat said tumor tissue at least 6°C. above the temperature of the adjacent normal tissue to cause necrosisof said tumor tissue, but insufficient to heat said adjacent normaltissue above 40° C. to cause significant damage to the adjacent normaltissue. .Iaddend. .Iadd.6. The method according to claim 5 wherein saidtumor tissue is heated in a range of 6° C. to 10° C. above thetemperature of the adjacent normal tissue. .Iaddend. .Iadd.7. The methodaccording to claim 5 wherein said radio frequency electromagnetic fieldis 13.56 megahertz. .Iaddend. .Iadd.8. A method of treating a naturallyoccurring tumor in a human comprising; placing a portion of the body ofthe human in which the tumor is located in a radio frequencyelectromagnetic field ranging in frequency from 100 kilohertz to 200megahertz, heating the tumor tissue in said portion of said body byabsorption of energy from said radio frequency electromagnetic field fora period of time and with intensity sufficient to cause necrosis of saidtumor, but insufficient to cause significant damage to the adjacentnormal tissue in said field. .Iaddend. .Iadd.9. A method of treating anaturally occurring tumor in a human comprising: placing a portion ofthe body of the human in which the tumor is located in a radio frequencyelectromagnetic field ranging in frequency from 100 kilohertz to lessthan 1000 megahertz, heating the tumor tissue in said portion of saidbody by absorption of energy from said radio frequency electromagneticfield for a period of time and with intensity sufficient to causenecrosis of said tumor, but insufficient to cause significant damage tothe adjacent normal tissue in said field. .Iaddend.